Adefovir accumulation and nephrotoxicity in renal interstitium: Role of organic anion transporters of kidney

Zhou, Yan; Yang, Yuquan; Wang, Pei; Wei, Mengmeng; Yue, Ma; Wu, Xinan

doi:10.1016/j.lfs.2019.03.042

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…The excretion of UA includes urate reabsorption and secretion. URAT1 and GLUT9 mainly participate in urate reabsorption, whereas OAT1 is an important mediator for primary renal urate secretion (So and Thorens, 2010;Zhou et al, 2019). Results indicated a significant decrease in the protein levels of URAT1 and GLUT9 and a distinct increase in those of OAT1 in SAL-treated groups compared to the HUA group, which was consistent with previous studies.…”

Section: Discussionsupporting

confidence: 90%

The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway

Chen

Jiang

et al. 2021

Front. Pharmacol.

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Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments.

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Section: Discussionsupporting

confidence: 90%

The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway

Chen

Jiang

et al. 2021

Front. Pharmacol.

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“…For this reason, ADV pretreated patients have a higher risk of developing chronic kidney failure, unlike naïve patients under TDF treatment. The role of ADV on nephrotoxicity was previous deepened in some studies with the evidence of interstitium brosis due to the drug accumulation outside the cells, when the tubular uptake was inhibited [14,15]. For this reason the interstitial damage due to ADV long term treatment can become chronic and irreversible, with a progressive reduction of eGFR in a large part of patients and the frequent evolution to interstitial nephritis and Fanconi syndrome [16].…”

Section: Discussionmentioning

confidence: 99%

Role of Plasmatic and Urinary Concentration of Tenofovir Disoproxil Fumarate in a Cohort of Patients Affected by Chronic Hepatitis B

Boglione

Benedetto

Dodaro

et al. 2021

Preprint

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The aim of this study was the evaluation of plasmatic and urinary therapeutic drug monitoring (TDM) of tenofovir disoproxil fumarate (TDF) in a cohort of patients affected by chronic hepatitis B (CHB). In 68 enrolled patients eGFR was 68 ml/min in naive, while in adefovir dipivoxil (ADV) pretreated patients was 55.5 ml/min (p<0.001). The HBV E genotype was related to lower TDF level (β= -0.698, p<0.001). Urinary TDF concentration was related to ADV pretreatment (β=0.829, p<0.001). TDF urinary concentrations maybe useful in clinical management of CHB patients with older age and previous treatment with ADV.

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“…Методики, использующиеся при исследовании накопления ЛС внутри клетки или мембранных микропузырьков, подходят для оценки взаимодействия ЛС с транспортерами -это дает информацию о возможном межлекарственном взаимодействии на уровне транспортеров. Ингибирование почечных транспортеров может привести к накоплению ЛС в клетке [9] или интерстиции в токсичных дозах [10].…”

Section: необходимые свойства клеточных систем для исследования нефротоксичностиunclassified

“…Еще один механизм токсичности -ингибирование транспортеров как частный случай межлекарственного взаимодействия. Ингибирование на уровне эффлюксных транспортеров может привести к токсическому накоплению вещества в эпителиальной клетке [9], если же ингибирование происходит на уровне инфлюксных транспортеров, токсические вещества могут накапливаться в интерстиции [10].…”

Section: механизмы нефротоксичностиunclassified

Experimental Cell Line Models for Nephrotoxicity Screening

Мазеркина¹,

Евтеев²,

Прокофьев³

et al. 2021

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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The aim of the study was to review literature data on cell models for experimental assessment of drug nephrotoxicity in vitro. Because of nephrotoxicity, 2% of new investigational medicinal products are discarded at the stage of preclinical in vivo studies in laboratory animals, and 19%—after phase 3 clinical trials. Prediction of toxicity in cell models could make drug development more cost-effective and help to reduce/avoid animal testing. At present, there are no official international guidelines for assessment of nephrotoxicity in vitro, but there is a lot of research underway. The main toxicity target in kidneys is renal proximal tubule epithelial cells, therefore the main research is focused on the development of renal proximal tubule epithelial cell lines with stable functional characteristics. Another important aspect in nephrotoxicity modeling is the choice of relevant test methods and end points which would reflect potential toxicity mechanisms. The paper reviews existing human renal proximal tubule epithelial cell lines and current test methods for assessing cytotoxicity. Promising areas for future development of cell models for nephrotoxicity assessment— are optimisation and standardisation of in vitro systems that would help to make preclinical predictions of drug nephrotoxicity in vivo.

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Adefovir accumulation and nephrotoxicity in renal interstitium: Role of organic anion transporters of kidney

Cited by 9 publications

References 28 publications

The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway

The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway

Role of Plasmatic and Urinary Concentration of Tenofovir Disoproxil Fumarate in a Cohort of Patients Affected by Chronic Hepatitis B

Experimental Cell Line Models for Nephrotoxicity Screening

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